Hypoxia and altered hemodynamic status, both components of myocardial infarction, have been shown to be potent inducers of the 70 kD family of heat shock proteins (HSP70). We hypothesized that after infarction, the surviving myocardium would synthesize HSP70 proteins in a temporally and regionally distinct pattern. We believed that there would be a lack of an HSP70 response in the infarcted area (I), reflecting the loss of viable cells. We further postulated that tissues bordering infarctions (M) would have a compromised HSP70 response. Conversely, we proposed that HSP70 would be induced in septal tissues (S) of the infarcted heart, as a hypertrophic adaptation. A rat model of myocardial infarction was used to examine the changes in relative concentration and distribution of three major HSP70 family proteins; cytoplasmic HSP72, mitochondrial HSP75, and endoplasmic reticular GRP78 (glucose regulated protein) during 21 days of recovery. While all three HSP70 family proteins investigated were detected in all hearts from all groups at all time periods, experimental treatment (infarction) induced changes in relative protein concentrations that varied with time and sample site location. Relative concentrations of HSP72 and GRP78 were unchanged in the 24 h following infarction while relative HSP75 concentrations were halved in M tissues during the same time period. Between days 5 and 7, several changes were noted. M samples displayed nearly twice the relative concentrations of HSP75 and GRP78 after infarction, but showed no change in HSP72. S tissues showed two-fold or larger increases in all three HSP70 family proteins. I samples showed unanticipated increases in HSP75 and GRP78 during this time period. After 14 to 21 days of recovery, HSP70 family protein concentration levels in M, S, and I tissues from infarcted hearts had returned to levels similar to those seen in control animals. We conclude that the myocardium is unable to, or does not, mount an immediate HSP70 response after infarction but does recover such activity by 5-7 days after infarction.

Animals↗

PubMedDate not supplied

Molecular modeling of phytochrome using constitutive C-phycocyanin from Fremyella diplosiphon as a putative structural template.

Phytochrome, the ubiquitous photosensor in green plants, is similar to C-phycocyanin in a number of ways. We have produced a model of the phytochrome chromophore binding pocket based on the X-ray crystal structure of C-phycocyanin from Fremyella diplosiphon [Duerring et al. (1991) J. Mol. Biol. 217, 577-592]. Twenty residues around the chromophore binding site of C-phycocyanin were changed to the corresponding residues of Avena phytochrome A for the modeling. In the minimized model, Arg-318, Ala-319, the methylene of Ser-322, Leu-325, Gln-326, and Tyr-327 (using the numbering of the Avena sequence; Cys-323 is chromophore bound) form a pocket on one side of the chromophore. The other side of the chromophore lacks hydrogen-bond donors and is involved only in van der Waals contact with the chromophore. The overall structure of the model may be described as one peptide segment "anchoring" the chromophore hydrophobically, covalently, and electrostatically from several directions, while the other key peptide segment simply provides a hydrophobic surface for the chromophore to rest against. The red light absorbing (Pr) chromophore of the model is buried more deeply in the binding pocket than the far red light absorbing (Pfr) chromophore. This apparently reflects reduced compatibility of the chromophore with the pocket upon photoisomerization, which requires the insertion of hydrophilic parts of ring D into the hydrophobic core of the protein. This concept is consistent with the experimental evidence that photoisomerization of the Pr chromophore is followed by movement of the chromophore from its binding pocket. In the proposed model, increased exposure of hydrophobic portions of the Pfr chromophore compared to the Pr chromophore is consistent with the red shift observed in the first intermediate of the Pr to Pfr photoconversion. The proposed model may be tested by mutation experiments, thus providing a viable model to foster the current rapid progress of molecular biology in this field.

Amino Acid Sequence↗

PubMedDate not supplied

Porcine antimicrobial peptides: new prospects for ancient molecules of host defense.

Antimicrobial peptides (AMPs) are small, endogenous, polycationic molecules that constitute a ubiquitous and significant component of innate immunity. These natural antibiotics have broad microbicidal activity against various bacteria, fungi, and enveloped viruses. Because most AMPs kill bacteria by physical disruption of cell membranes, which may prevent microorganisms from developing resistance against these agents, they are being explored as possible alternatives to conventional antibiotics. Pigs, like many other mammals, produce an impressive array of AMPs, which are synthesized predominantly by host leukocytic phagocytes or mucosal epithelial cells. Currently, more than a dozen distinct porcine AMPs have been identified and a majority belongs to the cathelicidin family. This review briefly summarizes recent advances in porcine AMP research with an emphasis on the diverse biological functions of each peptide. Mechanisms of action of these AMPs and their role in the resistance to infections are considered. Finally, the current status of pharmaceutical and agricultural uses of AMPs as well as future prospects for their application in the food animal industry is discussed.

Amino Acid Sequence↗